Our principal objective is to gain more insight into the mechanism of antibody production and, particularly, to explain the diversity of antibodies directed against a single, chemically well-defined antigenic determinant. During the prsent grant period we discovered that the hapten-specific antibodies directed against the p-azo-benzene-arsonate group in heterozygous a1a3 rabbits are expressed preferentially and almost exclusively in the allotype a1. In the same animals the simultaneously injected p-azobenzene-N-trimethylammonium hapten was expressed in both allotypes, a1 and a3, to approximately the same extent. We attribute tentatively the preferential expression of anti-As (As equals axobenzene-arsonate) in the a1 allotype to the strong affinity of the acidic As hapten for the strongly basic arginine residue which occurs in the 10-position of the VH region of the allotype a1, but is replaced in allotype a3 by either aspartic acid or valine. Our view is based on the fact that the specific combining site of the antibody molecules in also located in the the VH region of antibodies and thus is in the vicinity of position 10 in which the allotypes a1 and a3 differ from each other most drastically. Since homozygous a3 rabbits are able to produce a3-anti-As antibodies, we assume that the preference of a1 in the heterozygous rabbits is brought about by competition of the cell-bound receptors of the allotypes a1 and a3. In this competition the 10-arginine residue in allotype a1 increases the affinity of the a1-receptors for the As-hapten to such an extent that the As-hapten is bound predominantly by the a1 receptors and thus stimulates preferentially the cells which carry a1 receptors to mitosis and multiplication. The phenomenon of preferential expression of heterozygotes in one of two allotypes is obviously of general importance. It may be the reason why some human beings do and others do not produce antibodies against certain antigens or allergens. We intend to investigate further this interesting phenomenon.